Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2 carboxamide netropsin

Mrksich, Milan and Wade, Warren S. and Dwyer, Tammy J. and Geierstanger, Bernhard H. and Wemmer, David E. and Dervan, Peter B.
(1992)
Antiparallel side-by-side dimeric motif for sequence-specific recognition in the minor groove of DNA by the designed peptide 1-methylimidazole-2 carboxamide netropsin.
Proceedings of the National Academy of Sciences of the United States of America, 89
(16).
pp. 7586-7590.
ISSN 0027-8424.
PMCID PMC49755.
http://resolver.caltech.edu/CaltechAUTHORS:MRKpnas92

Abstract

The designed peptide 1-methylimidazole-2-carboxamide netropsin (2-ImN) binds specifically to the sequence 5'-TGACT-3'. Direct evidence from NMR spectroscopy is presented that this synthetic ligand binds DNA as a 2:1 complex, which reveals that the structure is an antiparallel dimer in the minor groove of DNA. This is in contrast to the 1:1 complexes usually seen with most crescent-shaped minor groove binding molecules targeted toward A+T-rich tracts but reminiscent of a dimeric motif found for distamycin at high concentrations. These results suggest that sequence-dependent groove width may play an important role in allowing an expanded set of DNA binding motifs for synthetic peptides.